CN100360159C - Kidney benefiting, Chong collateral reinforcing and menstruation regulating hemostat - Google Patents

Kidney benefiting, Chong collateral reinforcing and menstruation regulating hemostat Download PDF

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CN100360159C
CN100360159C CNB2004100198786A CN200410019878A CN100360159C CN 100360159 C CN100360159 C CN 100360159C CN B2004100198786 A CNB2004100198786 A CN B2004100198786A CN 200410019878 A CN200410019878 A CN 200410019878A CN 100360159 C CN100360159 C CN 100360159C
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radix
portions
blood
capsule
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CN1593500A (en
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张丽荣
王桂英
王齐
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HONGRENTANG PHARMACEUTICAL CO Ltd TIANJIN
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Abstract

The present invention relates to a medicine for benefiting kidneys, reinforcing actuation, regulating menstruation and stopping blood, which comprises the raw materials of prepared rehmanniae roots, panax pseudo-ginseng, tuckahoe, achyranthes roots, plantain seeds, schisandra fruits, bupleurum roots, cinnamon, water plantain, Chinese yams, coptis, tree peony barks and monkshood. After the traditional Chinese medicines are respectively extracted with water, pulverized, etc. according to different characteristics, the traditional Chinese medicines are proportionally prepared to make into hard capsules, tablets, drop pills, pills, granules, powder, decocted ointment, fluidextract and soaked ointment. The present invention has notable therapeutic effect.

Description

A kind of kidney tonifying CHONG meridian stabilizing and menstruation regulating haemostatic medicament
Technical field
The present invention relates to a kind of kidney tonifying CHONG meridian stabilizing and menstruation regulating haemostatic medicament compositions, particularly relating to a kind of kidney tonifying CHONG meridian stabilizing and menstruation regulating hemostasis that with the vegetable Chinese herbal medicine is raw material is made is used for because of deficiency of the liver and kindey, menorrhagia due to the Chong and Ren channel disorder, abdominal pain in menstruation, the adolescence dysfunctional uterine bleeding, last ring back metrorrhagia person's medicine and preparation thereof.
Background technology
At present, disclosed have June 4 1998 applying date about kidney tonifying CHONG meridian stabilizing and menstruation regulating haemostatic medicament and preparation thereof, and publication number 1203805 " a kind of health beverage of the woman's of control menopathy " is to be made by 29 flavor Chinese medicines; On June 10 1998 applying date, publication number 1206611 " Fukang granule for women of calming the nerves " is to be made by 20 flavor Chinese medicines, and flavour of a drug are many, cause the cost height.
Summary of the invention
The objective of the invention is to prepare the hemostasis of kidney tonifying CHONG meridian stabilizing and menstruation regulating with medicine of selecting meticulously and best proportioning is used for because of deficiency of the liver and kindey, menorrhagia due to the Chong and Ren channel disorder, abdominal pain in menstruation, adolescence dysfunctional uterine bleeding, last ring back metrorrhagia person's medicine and preparation thereof.
Solution of the present invention is based on motherland's medical science to menorrhagia, sick pathogenetic understanding of abdominal pain in menstruation and Therapeutic Principle, and the screening hemostasis, the pain relieving and the plant amedica of enriching blood by the theory of Chinese medical science prescription, skim the cream off milk, and make its performance kidney tonifying CHONG meridian stabilizing and menstruation regulating hemostatic effect.
(consumption is a weight portion) that medicine of the present invention also can be made by following component: 3~12 parts of Cortex Moutan 10-40 of Radix Rehmanniae Preparata 30-120 part Semen Plantaginis 12-48 part Poria 15~60 parts of Radix Bupleuri 10-40,6~24 portions of Rhizoma Alismatis of 15~60 portions of Cortex Cinnamomis of 15~60 parts of Fructus Schisandrae Chinensis of part Radix Achyranthis Bidentatae 10~40 portions of Radix Notoginseng 10-40 12~48 portions of Rhizoma Coptidis of 6~24 portions of Rhizoma Dioscoreaes of part Radix Aconiti Lateralis Preparata part
The optimum weight proportioning of medicine of the present invention is:
20 parts of 6 parts of Cortex Moutans of 30 parts of Fructus Schisandrae Chinensis of 20 parts of Radix Achyranthis Bidentataes of 30 parts of Radix Bupleuri of 24 parts of Poria of 60 portions of Semen Plantaginiss of Radix Rehmanniae Preparata, 24 portions of Rhizoma Coptidis of 12 portions of Rhizoma Dioscoreaes of 20 parts of Radix Aconiti Lateralis Preparatas of 20 portions of Radix Notoginseng of 12 portions of Rhizoma Alismatis of 30 parts of (system) Cortex Cinnamomis
With above-mentioned each component preparation cost invention medicine production method be: above 13 flavors, Radix Aconiti Lateralis Preparata, Radix Notoginseng, Radix Bupleuri, Cortex Cinnamomi, Rhizoma Coptidis powder are broken into fine powder, sieve mixing; Eight flavors such as all the other Radix Rehmanniae Preparata, Fructus Schisandrae Chinensis decoct with water three times, and 3 hours for the first time, 6 times of water gagings; 2 hours for the second time, 5 times of water gagings; 1 hour for the third time, 4 times of water gagings; Merging filtrate is condensed into relative density and is 1.25~1.30 thick paste, with above-mentioned powder mixing, makes granule, drying, and granulate incapsulates, promptly.Simultaneously, also can be made into soft capsule, tablet, drop pill, pill, granule, powder, soft extract, fluid extract and extractum.
Kidney tonifying CHONG meridian stabilizing and menstruation regulating haemostatic medicament of the present invention (also claiming " spring blood peace capsule ") has kidney tonifying Gu Chong, the regulating menstruation, hemostasis function through spring blood peace capsule pharmacological research, long term toxicity, evidence kidney tonifying CHONG meridian stabilizing and menstruation regulating haemostatic medicament such as clinical.Can be used for curing mainly: because of deficiency of the liver and kindey, the menorrhagia due to the Chong and Ren channel disorder, abdominal pain in menstruation, the adolescence dysfunctional uterine bleeding, last ring back metrorrhagia person's good medicine, and have no side effect.Test is as follows in detail:
Spring blood peace capsule pharmacological research
Summary: spring blood peace capsule is mainly used in treatment renal deficiency type adolescence dysfunctional uterine bleeding in clinical.Pharmacological experiment study shows that spring blood peace capsule gastric infusion can obviously shorten clotting time of mice; In stripped rabbit ear perfusion experiment, spring blood peace capsule has tangible vasoconstrictive effect; In the test of isolated rat uterus, can strengthen the irritability in uterus, strengthen its contractility.Through repeatedly gastric infusion mouse vagina plate coating checking and histopathologic examination, find that spring blood peace capsule can obviously improve mouse vagina epithelial cell keratinization rate, the vagina epithelium layer is thickened, basal layer cell and middle layer cells increase, and the epithelium keratinization is complete; Spring blood peace capsule repeatedly gastric infusion obviously increases mouse uterine weight.Histopathologic examination finds, makes the endometrium of mouse hypertrophy, presents secretory endometrium and changes.In sum, spring blood peace capsule clotting time by shortening, and vasoconstrictive improves the endocrine disturbance, regulate hormone level, and reach the purpose of treatment " anovulatory dysfunctional uterine hemorrhage ".
Test material
Medicine: the spring, blood peace capsule Tianjin Hongrentang Pharmaceutical Co., Ltd. provided.1g capsule medicated powder) and 1: 2 solution capsule medicated powder is boiled through twice 30 minutes warm fire, merge and to be made into 1: 1 solution (1ml solution:, be for experiment after decoct filters.
Animal: mice: the Kunming kind, female, body weight is shown test and is decided.
Rat: the wistar kind, female, body weight is shown test and is decided.
Rabbit: big white, female, the male dual-purpose of ear, body weight 2-3kg.
Test method and result:
One, blood is pacified the influence of capsule to clotting time of mice:
Get 30 of Healthy female mices, body weight 18-22g is divided into 2 groups at random, 15 every group.Spring blood peace administration group one twice-daily is irritated stomach and is given 1: 1 spring blood peace solution 28.8g/kg.Matched group gives distilled water, with reference to slide method [1]Cut off the Mus tail, get one and bleed, the immediate record clotting time the results are shown in Table 1.
Table 1 spring blood peace capsule is to the influence of clotting time of mice
Figure C20041001987800051
* P<0.01 (comparing) with matched group
Table 1 is the result show, clotting time of mice can be obviously shortened in spring blood peace capsule one twice-daily administration.
Two, spring blood is pacified the influence of capsule to the rabbit ear perfusion that exsomatizes:
6 of rabbit are selected in test for use,, the male and female dual-purpose.Every rabbit is selected the edge vein of picking up the ears for use, makes 6 specimen.Rabbit pentobarbital sodium (40mg/kg) ear vein is anaesthetized.The abdomen position is fixed on the operating-table, cuts off the hair of auris dextra root, and in rabbit ear convex surface center, as seen printing opacity has thick blood vessel to pass through.The larynx blood vessel moves towards to cut skin 2-3cm, separates subcutaneous tissue, promptly visible rabbit ear vein (central vein), and rabbit ear tremulous pulse is separated than the depths in parallel position with vein.The careful about 2cm length of rabbit ear tremulous pulse of separating is worn two rhizoid lines under it, the ligation near-end, and one " V " shape otch is made in the ligation distally again.The indenting ball that will be full of the syringe of Rockwell liquid and connect rubber tube inserts tremulous pulse rapidly, cuts off vein after the ligation, injects the blood that retains in the Rockwell liquid flushing blood vessel to intra-arterial, till effusive liquid is colourless.In the anesthesia of basal part of the ear surrounding injection procaine, cut the rabbit ear, the rabbit ear is fixed on five jiaos of glass plates, with 45 this plate is tilted to be fixed on the retort stand, rabbit ear arterial cannulation links to each other with the perfusion bottle of containing Rockwell liquid through rubber tube.Perfusate in water bath with thermostatic control to 37 ℃ and pass to mist.Regulate the rubber tube screw clamp, make the effusive perfusate of rabbit ear vein under glass plate angular flux, flow speed control is dripped number with the stopwatch record about 30 droplets/minute.Treated after the constant flow rate continuous record 3 minutes, its meansigma methods is a control value before the administration, slowly injects 1: 2 spring blood peace solution 1ml then from the intubate top, write down 3 minutes flow velocitys and gets its average and compare with administration is preceding, the results are shown in Table 2.
Table 2 spring blood peace capsule is to the influence of the rabbit ear perfusion flow that exsomatizes
Medicine Number of samples (individual) Rabbit ear perfusion flow (drip/minute)
Before the administration After the administration
Spring blood peace 6 31.83±5.33 26.50±6.88**
* P<0.01 (self compares before and after the administration)
Table 2 is the result show, 1: 2 spring blood peace solution can obviously reduce rabbit ear perfusion flow, has tangible vasoconstrictive effect.
Three. spring blood is pacified the influence of capsule to the isolated rat uterus: [3]
8 of unpregnancy female rats, body weight 180-230g are selected in test for use.Tested preceding 1 day, subcutaneous injection diethylstilbestrol 0.1mg/kg puts to death rat next day.Take out the uterus immediately and be dipped in the nutritional solution, nutritional solution adopts Geneu improvement tyrode's solution. [2]Choose cornua uteri and make 16 specimen, the water bath with thermostatic control temperature is 37 ± 0.5 ℃, and nutritional solution is used 15ml at every turn, feeds O 2Then the uterus specimen is connected on the lever adjustment of tonicity.The back adds 1: 1 spring blood peace solution 0.2ml to treat to shrink the uterus specimen steadily, traces uterus specimen contractile motion, the results are shown in Table 3.
Table 3 spring blood peace capsule is to the influence of isolated rat uterine smooth muscle contraction movement
"+" expression increases less than 50%, and " ++ " expression increases 50-100%, " +++" increase greater than 100%.
Table 3 is the result show, adds 1: 1 spring blood peace solution 0.2ml isolated rat uterine smooth muscle irritability is strengthened, and tension force increases, and amplitude strengthens.But to not obviously influence of frequency.
Four, spring blood is pacified the influence of capsule to vaginal epithelial cell: [4]
Choose the Healthy female mice, body weight 18-22g.All extract ovary, make vaginal smear examination, choose and be dioestrus 60 of mices in continuous 5 days.Be divided into 20 of 40 of administration groups and matched groups at random.The administration group is irritated stomach and given 28.8g/kg1: 1 spring blood peace solution, matched group gives distilled water, successive administration 15 days.All made vaginal smear examination behind the self administration of medication in the 5th day to the 15th day.Observing mouse vagina epithelial cell keratinization rate and histopathology changes.The results are shown in Table 4.
Table 4 spring blood peace capsule is to the influence of mouse vagina epithelial cell keratinization rate
Figure C20041001987800071
Table 4 result as seen, observe through the mouse vagina smear, the 8th day begins to occur changing after the administration, vaginal smear epithelial cell keratinization rate obviously improves, and being higher than 60% (height keratinization) has 10, and being lower than 60% (moderate keratinization) has 13, be lower than 30% (low keratinization) and have 13, between administration 8-10 days, mouse vagina epithelial cell keratinization rate obviously increases, and estrogen is in more than the medium level.The 8th day above level of moderate keratinization rate accounts for 36 and merely hit 23 to account for to account in 63.9%, the 9 day and accounted for 50% in 61%, the 10 day, and mouse vagina epithelial cell keratinization rate reduces gradually afterwards, accounts for 78.6% to the 15th day low keratinization.And matched group is the dioestrus change always, does not show the cycle variation.
Through histopathologic examination's discovery, put to death 8 mices on the 10th day after the administration, microscopy finds that the vagina epithelium layer thickens, and substrate stalk cell and middle layer cells increase, and the epithelium keratinization is complete or relatively more complete.Partially sliced visible cell silk splits phenomenon.And control group mice vagina epithelium layer is thinner, cells of superficial layer parakeratosis, and middle layer cells is bigger, and a matter is accompanied a large amount of leukocyte.Put to death whole mices after the administration on the 15th day, microscopy finds, except that 6 mouse vagina epithelial cell keratinization fully, all the other present vagina epithelium hamartoplasia more, but maturity is lower.Middle layer cells is thicker, and epithelium cells of superficial layer nuclear is bigger, is not differentiation fully.The cuticular layer on surface is rare, the more visible leukocyte of a matter.The microscopy result of matched group is consistent with the 10th day.
Five, spring blood is pacified the influence of capsule to uterus weight:
The female mice of extracing ovary is selected in test for use, and 18-22g is divided into three groups at random, and 15 of administration groups are irritated stomach by 28.8g/kg and given 1: 1 spring blood peace solution, and 15 of matched groups give distilled water, successive administration 15 days.9 of Progesterone groups, intramuscular injection every day 0.2mg/, successive administration 5 days.All after the last administration, put to death mice, win the uterus, weigh and the uterus weight in wet base, obtain the ratio of uterus weight in wet base (mg)/10g body weight, the results are shown in Table 5.
Table 5 spring blood peace capsule is to the influence of mouse uterine weight
△ △ P<0.01, * P<0.01 (comparing with matched group) (Progesterone and spring blood peace group are relatively) is table 5 result show, spring blood peace and Progesterone administration group and matched group more all can obviously increase the uterus weight in wet base of extracing the ovary mice, and the Progesterone group is better than spring blood peace administration group.
Six, spring blood is pacified endometrial influence:
After the above-mentioned off-test, in uterus stuck-at-0% formalin solution, paraffin section, endometrial variation is examined under a microscope in H.E dyeing.Put to death 8 mices of spring blood peace group on the 10th day after the administration, microscopy is found endometrial hyperplasia, and epithelium is high column, and nucleus occupies basilar part, the Interstitial cell dense arrangement.Put to death whole mices on the 15th day after the administration, spring blood peace group endometrium is the secretory phase change, and glandular epithelium is the doll shape, and nuclear cavity down appears in basal cell, and nuclear moves to the middle part, and the body of gland growth is short helical form bending, the visible secretions of part lumen of gland.Between matter more loose, cell is big slightly, endochylema is abundanter; The Progesterone group, neointimal hyperplasia is obvious, and glandular epithelium is the doll shape, the glandular tube hypertrophy, body of gland is long helical form.More be apparent that than spring blood peace group, the lumen of gland expansion, secretory activity is vigorous, and a matter is loose, and cell increases, and endochylema is abundant and transparent; And the attenuation of matched group endometrium, the cubic body of gland of glandular epithelium is arranged closely, and Interstitial cell is little, dense arrangement.Change as seen from the uterus, spring blood peace administration can present the inner membrance performance of propagation phase in early days, and the secretory endometrium similar to the Progesterone effect appearred on the 15th day in post-drug period to be changed.
Conclusion (of pressure testing): above pharmacological testing proves that spring blood peace capsule gastric infusion obviously shortens clotting time of mice; Spring blood peace has tangible vasoconstrictive effect in stripped rabbit ear perfusion experiment; In the test of isolated rat uterus, can strengthen the irritability in uterus, strengthen strength of uterine contraction; Through repeatedly gastric infusion mouse vagina plate coating checking and histopathologic examination, find how spring blood obviously improves mouse vagina epithelial cell keratinization rate.The vagina epithelium layer is thickened, and basal layer cell and middle layer cells increase, and the epithelium keratinization is complete; Spring blood peace capsule repeatedly gastric infusion obviously increases the Mouse Uterus weight in wet base, and histopathologic examination is carried out in the uterus, finds that spring blood peace can make the endometrium of mouse hypertrophy present secretory endometrium and change, and this variation is similar to the Progesterone effect.
Spring snow peace capsule long term toxicity test
Summary is entrusted by Jianjin Pharmaceutical Factory No. 5 of Traditional Chinese Medicines, observes spring snow peace capsule to rat continuous oral administration 90 long term toxicity tests.The result shows: each organizes body weight, biochemical indicator, hematological indices and the pathological observation of experimental animal.Toxic reaction does not all appear.100 times of high dose group behaviour clinical treatment amount.For clinical application safety and draft the human safe dose reference is provided.
Experiment material
One, animal: Wistar rat, 6 ages in week, body weight 90 ± 10g, totally 80 of male and female half and half.Available from Chinese Academy of Medical Sciences animal feeding center.The quality certification: the moving word 01-3008 raising condition of doctor: 5 in every cage, male and female divide supports.20 ℃-24 ℃ of room temperatures.Feeds utilized available from Chinese Academy of Medical Sciences animal feeding center.Drinking water is a tap water.
Two, medicine: spring snow peace capsule is provided by Tianjin Hongrentang Pharmaceutical Co., Ltd..Lot number: 000301
Three, instrument: the TBA-30FR of Toshiba biochemical instruments, Japanese blood counting instrument F-800.
Experimental technique
(1) dosage and grouping: divide four groups at random with the Wistar rat, 20 every group, male and female half and half.That is:
1, matched group: the distilled water that waits capacity
2, high dose group: 12g/kg
3, middle dosage group: 6g/kg
4, low dose group: 3g/kg
(2) route of administration and method:
Be mixed with suspension with distilled water and be used for gastric infusion.Volume 2ml/100g, be administered once every day, every morning 8:30-10:00, seven times weekly, successive administration 3 months (90 days).
(3) observation and test item:
1, overview: variations such as food-intake, body weight, behavioral activity, outward appearance sign, feces character.Administration front side body weight, routine weighing and adjust dosage (according to body weight change) weekly after the administration.
2, hematological indices: erythrocyte (RBC) counting, leukocyte (WBC) sum and classification, hemoglobin (Hb), platelet (Pit) clotting time (CT) are measured.
3, blood parameters:
Asparagine based transferase (GOT), alanine aminotransferase (GPT), alkali phosphatase (ALP), blood urea nitrogen (BUN), total protein (TP) albumin (ALB) blood glucose (GLU), total bilirubin (T-BTL), creatinine (Grea), T-CHOL (T-CHO)
4, system becomes celestial and histopathologic examination:
After used big genus becomes celestial and checks, take off the row histoorgan and do histological examination: the heart, liver, spleen, lung, kidney, stomach, duodenum, small intestinal, colon, adrenal gland, thymus, thyroid, pancreas, brain, hypophysis, breastbone, bladder, lymph node, testis, (attached testis) prostate, uterus, ovary, its center, liver, spleen, lung, kidney, adrenal gland, testis, (attached testis), uterus, (ovary), brain is weighed and calculate organ coefficient.
5, each index determining time:
At experiment the 90th day, each treated animal of etherization.Abdomen master A gets blood, and (about 2/3 is 12; 14 days (about 1/3 is 8) above-mentioned every indexs of complete detection are observed in drug withdrawal.
Experimental result:
1, overview:
Activities in rats, food-intake is normal, feces is normal, and each organizes the body weight no significant difference.(P>0.05) is as table 6
2, hematological examination: compare with matched group, the equal no significant difference of the every index of each administration group (P>0.05) is as table 7,8
3, blood biochemical analysis: each organizes the equal no significant difference of every blood biochemistry index (P>0.05) as table 9,10
4, internal organs inspection:
It is all normal that each organizes every internal organs system, and no significant difference (P>0.05) is as table 11,12
5, histopathologic examination:
(1) perusal: matched group and high, medium and low three each rat of dosage group are normal by hair, skin, crissum is not seen secretions, and breast, abdominal cavity do not see that pneumatosis, hydrops, serous coat are smooth, do not see the petechia, and each internal organs position is as usual.Perusal does not see that work becomes, and cuts off skull, and meninges and brain do not see that work becomes.
(2) histological examination: matched group and high, medium and low three dosage group rats are examined internal organs and the body of gland heart, liver, spleen, lung, kidney, stomach, brain, ileum, colon, bladder, uterus, ovary, testis, prostate, thymus, hypophysis, adrenal gland, thyroid etc. and there is no work and become.Part animal lung, kidney have the mild inflammation sexually transmitted disease (STD) to become, and are general pathological change, and not seeing has the specificity pathological change.Pathological changes does not have obvious degree difference between each group.(attached: pathology photo 1-22# is a matched group; 23-44# ties up high dose group)
Conclusion: 3 months rat long term toxicity tests of spring blood peace capsule.The result shows: rat dosage (high dose group) is 100 times of people's clinical treatment dosage, and successive administration did not see that obvious toxicity appearred in animal in 90 days.Pointed out the safety of clinical practice.
Experimental unit: Tianjin medical science institute pharmacology two Room study director: Li Meng
Experimenter: Li Meng, Wang Yan, Nie Wei, Wang Li, Guan Jingfang, Bao Huairu
Table 6 spring is learned the influence (X ± SD, n=12 or n=8) of peace capsule to rat body weight
Group Body weight change X ± SD (g) before and after the administration, n=12 14 days n=8 after the drug withdrawal
0 week 1 week 2 weeks 3 weeks 4 weeks 5 weeks 6 weeks 7 weeks 8 weeks 9 weeks 10 weeks 11 weeks 12 weeks 13 weeks 15 weeks
Matched group 87.0 ±9.3 95.6 ±15.8 114.7 ±23.6 123.9 ±24.8 140.1 ±22.9 157.1 ±35.4 171.1 ±34.8 186.1 ±35.6 195.4 ±45.9 210.1 ±45.1 226.0 ±47.9 249.8 ±51.8 276.5 ±52.3 299.9 ±50.9 319. 1 ± 57.7
High dose 84.2 ±8.5 99.5 ±17.3 118.3 ±27.4 130.7 ±25.3 148.3 ±26.4 163.4 ±25.1 178.2 ±36.4 187.6 ±34.5 195.8 ±29.6 209.5 ±26.8 236.8 ±40.9 251.3 ±45.2 281.3 ±42.0 294.4 ±48.6 310. 8 ± 66.3
Middle dosage 85.2 ±9.0 105.1 ±15.6 120.7 ±28.9 134.5 ±28.5 150.3 ±23.8 163.6 ±29.7 174.6 ±37.2 180.1 ±35.1 199.1 ±45.5 204.8 ±38.1 222.5 ±39.9 255.3 ±36.9 273.6 ±41.3 285.6 ±52.4 302. 1 ± 45.8
Low dosage 86.1 ±14.6 94.7 ±14.6 114.8 ±21.7 129.6 ±20.4 143.9 ±25.8 158.7 ±24.9 168.6 ±35.7 180.7 ±35.3 192.9 ±35.8 218.4 ±45.3 243.9 ±32.1 251.8 ±45.0 278.2 ±42.7 292.8 ±53.4 315. 4 ± 49.7
Compare no significant difference (P>0.05) with matched group
Table 7 spring is learned the influence (X ± SD, n=12 are only) to the every hematological indices of rat after 90 days of the continuous gastric infusion of peace capsule
Group Hemogram The WBC classification Clotting time
RBC×10 12 Hbg/l Pit×10 9/l WBC×10 9/l Neutral % Lymph % CT(S)
Matched group 7.1±0.8 139.0±17.6 420.5±49.3 13.5±3.9 0.4±0.1 0.6±0.1 44.5±9.6
High dose 7.0±0.7 135.4±21.8 392.4±53.6 14.3±4.5 0.4±0.1 0.6±0.1 40.2±8.9
Middle dosage 6.9±0.6 140.6±19.5 401.6±73.5 13.9±3.7 0.3±0.1 0.7±0.1 39.6±6.0
Low dosage 6.9±0.5 145.0±19.8 413.6±64.7 14.5±4.8 0.3±0.1 0.7±0.1 45.3±9.8
Compare no significant difference (P>0.05) with matched group
Table 8 spring snow is pacified capsule drug withdrawal influence (X ± SD, n=8 are only) to the every hematological indices of rat after 14 days
Group Hemogram The WBC classification Clotting time
RBC×10 12 Hbg/l Pit×10 9/1 WBC×10 9/1 Neutral % Lymph % CT(S)
Matched group 7.1±0.8 139.0±17.6 420.5±49.3 13.5±3.9 0.4±0.1 0.6±0.1 44.5±9.6
High dose 7.0±0.7 135.4±21.8 392.4±5 3.6 14.3±4.5 0.4±0.1 0.6±0.1 40.2±8.9
Middle dosage 6.9±0.6 140.6±19.5 401.6±73.5 13.9±3.7 0.3±0.1 0.7±0.1 39.6±6.0
Low dosage 6.9±0.5 145.0±19.8 413.6±64.7 14.5±4.8 0.3±0.1 0.7±0.1 45.3±9.8
Compare no significant difference (P>0.05) with matched group
The table 9 spring snow peace continuous gastric infusion of the capsule influence to the every index biochemistry of rat in 90 days (X ± SD, n=12 are only)
The project group GPT (U/L) GOT (U/L) ALP (U/L) BUN (mg/dl) T.P (g/dl) Alb (g/dl) GLU (mg/dl) Crea (mg/dl) T-Cho (mg/dl) T-Bil (mg/dl)
Matched group 34.1±6.8 161.4± 28.7 57.9± 16.3 21.2±4.2 7.3±0.8 3.1±0.3 87.0± 14.2 1.5±0.2 74.8± 14.4 0.20± 0.04
High dose 34.9±9.9 168.2± 25.7 52.7± 13.2 20.3±3.2 7.0±0.9 3.2±0.3 83.2± 13.0 1.5±0.2 74.2± 15.3 0.21± 0.09
Middle dosage 36.7±8.4 167.4± 18.3 54.8± 10.9 21.4±2.3 7.8±0.6 3.1±0.4 81.7± 18.4 1.5±0.1 70.1± 11.6 0.20± 0.07
Low dosage 32.8±8.5 161.0± 17.4 59.4± 17.1 23.8±4.3 7.2±0.8 3.2±0.5 86.2± 14.9 1.4±0.2 72.8± 16.8 0.19± 0.06
Compare no significant difference (p>0.05) with matched group
Table 10 spring snow is pacified capsule drug withdrawal influence (X ± SD, n=8 are only) to the every biochemical indicator of rat after 14 days
Compare no significant difference (p>0.05) with matched group
The continuous gastric infusion of table 11 spring snow peace capsule after 90 days to the sparse influence of Rats Organs and Tissues (X ± SD, n=12 are only)
Group The heart Lung Liver Spleen The adrenal gland Kidney Testis (epididymis) (6) Uterus (ovary) (6) Brain
Matched group 0.96±0.12 0.35% 1.34±0.20 0.48% 9.48±1.19 3.4% 0.65 ± 0.08 0.23% 0.035± 0.009 0.013% 1.64±0.20 0.95% 3.16±0.36 0.78% 0.75±0.03 0.272% 1.68±0.24 0.61%
High dose 1.09±0.18 0.4% 1.28±0.18 0.47% 9.57±1.02 3.54% 0.62 ± 0.06 0.22% 0.036± 0.006 0.013% 1.59±0.12 0.96% 3.24±0.16 0.83% 0.72±0.08 0.166% 1.71±0.16 0.63%
Middle dosage 0.97±0.14 0.4% 1.23±0.13 0.45% 8.60±1.03 3.11% 0.56 ± 0.07 0.20% 0.036± 0.009 0.013% 1.48±0.13 0.90% 3.15±0.11 0.78% 0.72±0.05 0.261% 1.67±0.18 0.61%
Low dosage 0.99±0.17 0.36% 1.29±0.18 0.46% 8.97±0.91 3.21% 0.55 ± 0.05 0.20% 0.035± 0.006 0.013% 1.51±0.10 0.90% 3.13±0.10 0.76% 0.73±0.03 0.262% 1.74±0.22 0.62%
Compare no significant difference (p>0.05) with matched group
The drug withdrawal of table 12 spring snow peace capsule after 14 days to the sparse influence of Rats Organs and Tissues (X ± SD, n=8 are only)
Group The heart Lung Liver Spleen The adrenal gland Kidney Testis (epididymis) (6) Uterus (ovary) (6) Brain
Matched group 1.00±0.18 0..32% 1.34±0.24 0.43% 11.29±2.64 3.63% 0.61±1.03 0.20% 0.035± 0.009 0.011% 1.80±0.22 0.90% 3.57±0.20 0.83% 0.82±0.12 0.264% 1.83±0.22 0.59%
High dose 1.06±0.19 0.34% 1.37±0.14 0.44% 11.72±2.58 3.79% 0.59±0.04 0.19% 0.036± 0.006 0.012% 1.78±0.26 0.90% 3.39±0.13 0.77% 0.82±0.22 0.265% 1.84±0.23 0.60%
Middle dosage 1.06±0.18 0.35% 1.34±0.25 0.44% 11.74±3.48 3.82% 0.59±0.02 0.19% 0.036± 0.004 0.011% 1.76±0.18 0.90% 3.46±0.24 0.80% 0.83±0.12 0.270% 1.83±0.33 0.60%
Low dosage 1.03± 0.19 0.34% 1.34± 0.23 0.44% 11.68± 2.45 3.89% 0.60± 0.03 0.20% 0.035± 0.006 0.011% 1.79± 0.25 0.90% 3.58± 0.11 0.84% 0.80± 0.13 0.261% 1.81± 0.13 0.59%
Compare no significant difference (p>0.05) with matched group
Clinical report to diseases such as spring blood peace capsule for treating dysfunctional uterine hemorrhages
Summary: test objective: the clinical efficacy and the safety of diseases such as spring blood peace capsule for treating dysfunctional uterine hemorrhage and menoxenia are investigated.Test method: adopt the out-patient clinic and hospitalization patient is divided into treatment group and matched group at random, compare observation.Result of the test: spring blood peace capsule for treating 220 routine patients have tangible curative effect to the improvement of its symptom than matched group.And the rising to hematochrome has certain effect.The safety indexes detection has all been done in this test, proves hepatic and renal function is had no effect, and does not have other side effect.
Key word: spring blood peace capsule dysfunctional uterine hemorrhage menoxenia clinical research
1. case choice criteria
1.1 diagnostic criteria
1.1.1 Western medicine diagnose standard
(1) anovulatory functional bleeding: because ovulation failure, no corpus luteum forms, and endometrial hyperplasia is too much, the irregular metrorrhagia of clinical manifestation, and menstrual period are different in size, and are few for a long time during amount of bleeding, even bleed profusely.Gynecologial examination: cervix uteri hyperemia when hemorrhage, softer, palace mouth pine, uterus are softer, have with a side or the increase of bilateral ovaries capsule.The basal body temperature single phase property, the vaginal exfoliated cell smear anovulatory cycle sexually revises, and hemorrhage preceding 1-2 days cervix uteri mucus presents the lobate crystallization of pteridophyte, and the visible proliferative phase of inner membrance pathologic finding changes or Swiss cheese hyperplasia, and the no secretory phase changes.
(2) ovulation type anovulatory dysfunctional uterine hemorrhage: 1. luteal insufficiency: through preceding endometrial secretion dysfunction; The clinical manifestation menstrual cycle shortens, and how much differs menostaxis through amount; The visible sometimes keratinocyte index of vaginal smear is higher, and cell accumulation, gauffer are not good; The basal body temperature biphasic or bipolar type, shorten luteal phase, below 10 days, or is trapezoidal rising or decline.2. atrophy of corpus iuteum is incomplete, is the secretory phase change through intrauterine film biopsy in the 5th day; Clinical manifestation is that menstrual cycle is normal, and how many menostaxis differs through amount; Basal body temperature is the biphasic or bipolar type that is not true to type, fall delay or decline gradually.
1.1.2 tcm diagnosis standard
1.1.2.1 Chinese medical discrimination: kidney yang deficiency syndrome (with reference to " new Chinese medicine clinical guidance principle ")
(1) hemorrhage suddenly, amount is many or not to the utmost dripping, and color is light or dark red, and matter is rare clearly.
(2) abdominal pain in menstruation, the cold or empty discomfort of weighing down of lower abdomen.
(3) lethargy.
(4) dizzy, stomachache.
(5) shallow complexion.
(6) clear urine in large amounts, big loose stool is thin.
(7) fat light, the white and thin fur of body of the tongue.
(8) deep,thready and forceless pulse.
More than (1), (2) must possess, have concurrently all the other 4 promptly diagnosable.
1.1.2.2 mild symptoms weight classification standard sees Table 13
Table 13
Symptom Gently In Heavy
Amount of bleeding is many Wrap dripping not to the utmost 5-7 days with paper one every day Wrap dripping not to the utmost 7-10 days with paper two every day Use the paper three guarantees every day, dripping not to the utmost more than 10 days
Abdominal pain in menstruation Stomachache can be stood Stomachache needs to have a rest The thing pain relieving of need taking medicine
The spirit Mi that withers Fatigue and weak Lassitude Drowsy
Dizzy Idol has dizzy Dizzyly need not have a rest Need bed
Shallow complexion White The sallow profit of owing Sallow and dark
Clear urine in large amounts, big loose stool is thin Every day 2-3 time Every day 4-5 time Every day is more than 5 times
Body of the tongue is fat light, white and thin fur Pale tongue, white and thin fur Corpulent tongue matter is light, and tongue is little greasy Enlarged tongue is light, gums, and tongue is greasy in vain
Deep,thready and forceless pulse Carefully unable Heavy unable Heavy carefully unable
Hematochrome 10g 8g 6g
The nail fold microcirculation Slight blood stasis The moderate blood stasis The severe blood stasis
1.2 include the case standard in:
In meeting, Western medicine diagnose standard and Chinese medical discrimination typing standard and go up the ring seraglio blood person of increasing, all can include the test case in.
1.3 get rid of the case standard:
(1) confirms by gestation tumor, wound or whole body mathematics disease causer on inspection.
(2) age is person below 14 years old or more than 50 years old, or women breast-feeding their children, to this medicine allergy sufferers.
(3) be associated with serious primary disease such as cardiovascular, liver, kidney and hemopoietic system, psychotic.
(4) do not meet the standard of including in, not medication in accordance with regulations can't be judged that curative effect or data are not congruent to affect the treatment or safety judgement person.
2. observation index:
2.1 safety observation index:
2.1.1 general health check-up project
2.2 health giving quality observation index:
2.2.1 treatment group and matched group doing well,improving contrast situation
3. EXPERIMENTAL DESIGN
3.1 medicine:
Treatment group: spring blood peace capsule
Matched group: YIMU TIAOJING WAN
3.2 usage: treatment group: oral, one time 4,3 times on the one.
The treatment group: oral, one time 4,3 times on the one.
Matched group: oral, one time 10 ball, 1-3 time on the one.
3.3 the course of treatment: be a course of treatment all around, observed for two courses of treatment continuously.
3.4 treatment requires: do not add during the medication with hemostasis, the pain relieving and the medicine of enriching blood are in order to avoid influence is judged when analyzing curative effect.
3.5 observed and recorded, summary require:
By the clinical study design requirement, unified form is made itemized record, conscientiously finishes writing case history, should note observing untoward reaction, and tracing study.After the off-test, can not alter case history arbitrarily, various data must be done statistical procedures.
4. curative effect determinate standard:
4.1 traditional Chinese medical science disease curative effect determinate standard
4.1.1 clinical recovery: after the control over bleeding, continuous 3 menstrual cycle, menstrual period, blood volume are all normal, and subjective symptoms disappears, and hematochrome can recover normally to ovulate more than 10g, is no less than 12 days luteal phase.
4.1.2 produce effects: after the control over bleeding, menstrual cycle, blood volume are normal substantially, but menstrual period still at 7-10 days, subjective symptoms disappears substantially, hematochrome is the above person of 10g.
4.1.3 effectively: menstrual cycle, menstrual period, part subjective symptoms be improved significantly, oligemia, hematochrome is the above person of 8g.
4.1.4 it is invalid: above every improvement of all not having.
4.2 safety evaluatio standard
One-level: safety, there is not any untoward reaction.
Secondary: compare safety,, need not do any processing, can continue administration if any untoward reaction.
Three grades: safety problem is arranged, moderate untoward reaction is arranged, can continue administration after processing.
Level Four: because of test is ended in untoward reaction.
5. statistical procedures:
Measurement data adopts the t check
6. clinical physical data
6.1 the case source: select my the special outpatient clinic patient of institute 300 examples, wherein 220 examples are organized in treatment, matched group 80 examples.
6.2 wedding is denied, age distribution, sees Table 14
Table 14 a liang group patient wedding is denied, the age structure distribution table
The example number Married Unmarried Below 20 years old 20 years old- 30 years old- 40 years old-
The treatment group 220 109 111 101 65 27 27
Matched group 80 38 42 36 24 10 10
Two groups of patients wedding not, age ratio, through X 2Check P>0.05, difference does not have significance, has comparability.
6.3 sick the kind: clinical symptoms relatively sees Table 15 before two groups of patient treatments
The sick kind of table 15 liang group patient distributes relatively
The example number Amount of bleeding is many Abdominal pain in menstruation Lethargy Dizzy Shallow complexion
The treatment group 220 220 220 124 151 188
Matched group 80 80 80 50 58 64
Clinical symptoms compares before two groups of patient treatments, through X 2Check P>0.05, difference does not have significance, has comparability.
7. interpretation of result
7. interpretation of result
7.1 two groups of patient's clinical symptoms curative effects relatively, sees Table 16.
7.2 safety indexes detects before and after the treatment of treatment group, sees Table 17.
Table 16 liang group patient clinical symptoms curative effect relatively
Amount of bleeding is many Abdominal pain in menstruation Lethargy Dizzy Shallow complexion
Treatment group matched group Recovery from illness produce effects enabledisable efficient (%) recovery from illness produce effects enabledisable efficient (%) 64 72 69 15 93.18 21 21 24 14 82.5 59 65 72 24 89.1 20 19 24 17 78.75 36 34 42 12 90.3 15 14 13 8 84.0 37 42 45 27 82.12 13 15 16 14 75.86 49 64 57 18 90.4 20 16 19 9 85.94
Two groups of patient's clinical symptoms curative effects are through X 2Check P<0.01, difference has significance.
Safety indexes detects before and after the treatment of table 17 treatment group
Before controlling After controlling
Routine blood test Normally 220 220
Unusually 0 0
Routine urinalysis Normally 220 220
Unusually 0 0
Just conventional Normally 220 220
Unusually 0 0
Rabat Normally 220 220
Unusually 0 0
Electrocardiogram Normally 220 220
Unusually 0 0
GPT Normally 220 220
Unusually 0 0
BUN Cr Normally 220 220
Unusually 0 0
Before and after the treatment group treatment to all patients do blood, urine, just conventional sense and electrocardiogram liver, renal function detect, the result does not find These parameters is had a significant effect.
8. untoward reaction
This tests no any untoward reaction among the 360 routine patients, and the safety evaluatio standard is an one-level.
9. rejecting case
This test does not have the case of rejecting.
10. follow up a case by regular visits to
The above case of produce effects is carried out the trimestral statistics of following up a case by regular visits to, see Table 18.
Table 18 Follow-up results
Add up to Follow up a case by regular visits to case load Recurrence Not recurrence
220 100 0 100
11, discussion, brief summary:
The spring blood peace capsule that Tianjin Hongrentang Pharmaceutical Co., Ltd. produces has kidney tonifying Gu Chong, the effect of regulating menstruation, hemostasis.Be mainly used in because of deficiency of the liver and kindey the menorrhagia due to the Chong and Ren channel disorder, abdominal pain in menstruation, adolescence dysfunctional uterine bleeding, last ring back metrorrhagia person.The clinical observation to above disease 220 routine patients is passed through by my institute, prove that this product all has significantly curative effect to improving diseases such as dysfunctional uterine hemorrhage and abdominal pain in menstruation, treatment group and matched group are learned processing P<0.05 by statistics, and there were significant differences, and it is reliable by its safety of clinical proof, human body is had no side effect, should extensively promote the use of.
The clinical observation of spring blood peace capsule for treating dysfunctional uterine hemorrhage
Summary: test objective: the spring clinical efficacy and the safety of blood peace capsule for treating dysfunctional uterine hemorrhage investigated.Test method: adopt the out-patient clinic and hospitalization patient is divided into treatment group and matched group at random, compare observation.Result of the test: spring blood peace capsule for treating dysfunctional uterine hemorrhage 180 examples, the improvement of its symptom there is tangible curative effect than matched group, wherein treatment is organized clinical total effective rate and is reached 97.78%.And the rising to hematochrome has certain effect.The safety indexes detection has all been done in this test, proves hepatic and renal function is had no effect, and does not have other side effect.
Key word: spring blood peace capsule dysfunctional uterine hemorrhage clinical research
7. case choice criteria
1.1 diagnostic criteria
1.1.1 Western medicine diagnose standard
(3) anovulatory functional bleeding: because ovulation failure, no corpus luteum forms, and endometrial hyperplasia is too much, the irregular metrorrhagia of clinical manifestation, and menstrual period are different in size, and are few for a long time during amount of bleeding, even bleed profusely.Gynecologial examination: cervix uteri hyperemia when hemorrhage, softer, palace mouth pine, uterus are softer, have with a side or the increase of bilateral ovaries capsule.The basal body temperature single phase property, the vaginal exfoliated cell smear anovulatory cycle sexually revises, and hemorrhage preceding 1-2 days cervix uteri mucus presents the lobate crystallization of pteridophyte, and the visible proliferative phase of inner membrance pathologic finding changes or Swiss cheese hyperplasia, and the no secretory phase changes.
(4) ovulation type anovulatory dysfunctional uterine hemorrhage: 1. luteal insufficiency: through preceding endometrial secretion dysfunction; The clinical manifestation menstrual cycle shortens, and how much differs menostaxis through amount; The visible sometimes keratinocyte index of vaginal smear is higher, and cell accumulation, gauffer are not good; The basal body temperature biphasic or bipolar type, shorten luteal phase, below 10 days, or is trapezoidal rising or decline.2. atrophy of corpus iuteum is incomplete, is the secretory phase change through intrauterine film biopsy in the 5th day; Clinical manifestation is that menstrual cycle is normal, and how many menostaxis differs through amount; Basal body temperature is the biphasic or bipolar type that is not true to type, fall delay or decline gradually.
1.1.2 tcm diagnosis standard
1.1.2.1 Chinese medical discrimination: kidney yang deficiency syndrome (with reference to " new Chinese medicine clinical guidance principle ")
(9) hemorrhage suddenly, amount is many or not to the utmost dripping, and color is light or dark red, and matter is rare clearly.
(10) abdominal pain in menstruation, the cold or empty discomfort of weighing down of lower abdomen.
(11) lethargy.
(12) dizzy, stomachache.
(13) shallow complexion.
(14) clear urine in large amounts, big loose stool is thin.
(15) fat light, the white and thin fur of body of the tongue.
(16) deep,thready and forceless pulse.
More than (1), (2) must possess, have concurrently all the other 4 promptly diagnosable.
1.1.2.2 mild symptoms weight classification standard sees Table 19
Table 19
Symptom Gently In Heavy
Primary symptom 2 minutes 4 minutes 6 minutes
Amount of bleeding is many Wrap dripping not to the utmost 5-7 days with paper one every day Wrap dripping not to the utmost 7-10 days with paper two every day Use the paper three guarantees every day, dripping not to the utmost more than 10 days
Abdominal pain in menstruation Stomachache can be stood Stomachache needs to have a rest The thing pain relieving of need taking medicine
Lethargy Fatigue and weak Lassitude Drowsy
Dizzy Idol has dizzy Dizzyly need not have a rest Need bed
Shallow complexion White The sallow profit of owing Sallow and dark
Clear urine in large amounts, big loose stool is thin Every day 2-3 time Every day 4-5 time Every day is more than 5 times
Body of the tongue is fat light, white and thin fur Pale tongue, white and thin fur Corpulent tongue matter is light, and tongue is little greasy Enlarged tongue is light, gums, and tongue is greasy in vain
Deep,thready and forceless pulse Carefully unable Heavy unable Heavy carefully unable
Hematochrome 10g 8g 6g
The nail fold microcirculation Slight blood stasis The moderate blood stasis The severe blood stasis
1.1.2.3 state of an illness grade scale:
Slightly: disease integrated value summation 8-18 branch
Moderate: disease integrated value summation 19-36 branch
Severe: disease integrated value summation 〉=37 minutes
1.2 include the case standard in:
In meeting, Western medicine diagnose standard and Chinese medical discrimination typing standard and go up the ring seraglio blood person of increasing, all can include the test case in.
1.3 get rid of the case standard:
(1) confirms by gestation tumor, wound or whole body mathematics disease causer on inspection.
(2) age is person below 14 years old or more than 50 years old, or women breast-feeding their children, to this medicine allergy sufferers.
(3) be associated with serious primary disease such as cardiovascular, liver, kidney and hemopoietic system, psychotic.
(4) do not meet the standard of including in, not medication in accordance with regulations can't be judged that curative effect or data are not congruent to affect the treatment or safety judgement person.
8. observation index:
2.1 safety observation index:
2.1.1 general health check-up project
2.2 health giving quality observation index:
2.2.1 treatment group and matched group doing well,improving contrast situation
9. EXPERIMENTAL DESIGN
3.1 medicine:
Treatment group: spring blood peace capsule
Matched group: YIMU TIAOJING WAN
3.5 usage:
The treatment group: oral, one time 4,3 times on the one.
Matched group: oral, one time 10 ball, 1-3 time on the one.
3.6 the course of treatment: be a course of treatment all around, observed for two courses of treatment continuously.
3.7 treatment requires:
Do not add during the medication with hemostasis, the pain relieving and the medicine of enriching blood are in order to avoid influence is judged when analyzing curative effect.
3.5 observed and recorded, summary require:
By the clinical study design requirement, unified form is made itemized record, conscientiously finishes writing case history, should note observing untoward reaction, and tracing study.After the off-test, can not alter case history arbitrarily, various data must be done statistical procedures.
10. curative effect determinate standard:
4.2 traditional Chinese medical science disease curative effect determinate standard
4.1.1 clinical recovery: after the control over bleeding, continuous 3 menstrual cycle, menstrual period, blood volume are all normal, and subjective symptoms disappears, and hematochrome can recover normally to ovulate more than 10g, is no less than 12 days luteal phase.
4.1.2 produce effects: after the control over bleeding, menstrual cycle, blood volume are normal substantially, but menstrual period still at 7-10 days, subjective symptoms disappears substantially, hematochrome is the above person of 10g.
4.1.3 effectively: menstrual cycle, menstrual period, part subjective symptoms be improved significantly, oligemia, hematochrome is the above person of 8g.
4.1.4 it is invalid: above every improvement of all not having.
4.2 safety evaluatio standard
One-level: safety, there is not any untoward reaction.
Secondary: compare safety,, need not do any processing, can continue administration if any untoward reaction.
Three grades: safety problem is arranged, moderate untoward reaction is arranged, can continue administration after processing.
Level Four: because of test is ended in untoward reaction.
11. statistical procedures:
Measurement data adopts the t check
12. clinical physical data
6.1 the case source: select my the special outpatient clinic patient of institute 360 examples, wherein 180 examples are organized in treatment, matched group 180 examples.
6.3 wedding is denied, age distribution sees Table 20:
Table 20 a liang group patient wedding is denied, the age structure distribution table
The example number Married Unmarried Below 20 years old 20 years old- 30 years old- 40 years old-
Treatment group matched group 180 180 85 84 95 96 83 80 53 54 22 23 22 23
Two groups of patients wedding not, age ratio, through X 2Check P>0.05, difference does not have significance, has comparability.
6.3 symptom integral distributes before two groups of patient treatments, sees Table 21.
Clinical symptoms integration situation before the table 21 liang group treatment (X ± SD)
The treatment group Matched group The P value
Reciprocal Integration Reciprocal Integration
The dizzy shallow complexion of many abdominal pain in menstruation of integration amount of bleeding lethargy 180 180 180 102 124 154 4.21±1.12 5.41±2.05 3.31±1.65 4.05±1.24 3.35±2.01 4.21±1.15 180 180 180 112 131 143 4.28±1.17 5.38±2.24 3.40±1.25 4.13±1.14 3.42±2.11 4.35±1.07 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
Clinical symptoms integration situation compares before two groups of treatments, through X 2Check P>0.05, difference does not have significance, has comparability.
7. interpretation of result
7.1 two groups of efficacy analysis see Table 22
Table 22 liang group patient clinical efficacy relatively
Treatment group (180 example) Matched group (180 example)
Recovery from illness produce effects enabledisable total effective rate (%) 65 61 50 4 97.78 53 46 55 26 85.56
Two groups of patient's clinical symptoms curative effects are through X 2Check P<0.01, difference has significance.
7.3 symptom integral relatively sees Table 23 behind two groups of patient treatments.
Symptom integral comparison behind the table 23 liang group patient treatment (X ± SD)
The treatment group Matched group The P value
Reciprocal Integration Reciprocal Integration
The dizzy shallow complexion of many abdominal pain in menstruation of amount of bleeding lethargy 180 180 102 124 154 3.16±0.74 3.66±1.41 2.01±0.12 3.01±1.02 2.51±1.43 180 180 112 131 143 3.98±0.84 4.52±1.56 3.21±0.82 3.99±1.23 2.86±1.63 <0.05 <0.05 <0.05 <0.05 <0.05
Symptom integral relatively through statistics P<0.05, shows that spring blood peace capsule is better than YIMU TIAOJING WAN behind two groups of patient treatments, and two groups have significant difference.
10. untoward reaction
This tests no any untoward reaction among the 360 routine patients, and the safety evaluatio standard is an one-level.
11. rejecting case
This test does not have the case of rejecting.
12. discussion, brief summary:
The spring blood peace capsule of being produced by Tianjin Hongrentang Pharmaceutical Co., Ltd. has kidney tonifying Gu Chong, the effect of regulating menstruation, hemostasis.Be mainly used in because of liver
Menorrhagia due to the kidney deficiency, Chong and Ren channel disorder, abdominal pain in menstruation, adolescence dysfunctional uterine bleeding, last ring back metrorrhagia person.The clinical observation to above disease 180 routine patients is passed through by my institute, prove that this product has significantly curative effect to improving aspects such as dysfunctional uterine hemorrhage, promotion microcirculation, treatment group and matched group are learned by statistics and are handled P<0.05, and it is reliable by its safety of clinical proof, human body is had no side effect, should extensively promote the use of.
Tianjin College of Traditional Chinese Medicine two attached internal medicine
The clinical summary of spring blood peace capsule for treating dysfunctional uterine hemorrhage:
Descriptor: spring blood peace capsule dysfunctional uterine hemorrhage curative effect observation clinical research summary: test objective: the clinical efficacy and the safety of the dysfunctional uterine hemorrhage of spring blood peace capsule for treating kidney yang deficiency syndrome are investigated.Test method: the method that adopts self cross-reference.Result of the test: spring blood peace capsule for treating kidney yang deficiency syndrome dysfunctional uterine hemorrhage 300 examples, the improvement of its symptom there is tangible curative effect, wherein clinical recovery 108 examples account for 36%; Produce effects 102 examples account for 34%; Effective 84 examples account for 28%; Invalid 6 examples account for 2%.Learn by statistics and handle P<0.05.And the hematochrome situation of change before and after the treatment observed, prove can haematochrome increasing, learns processing P<0.01 by statistics.This is tested among the 300 routine patients and has all done the safety indexes detection, proves hepatic and renal function is had no effect, and does not have other side effect.
13. case choice criteria
1.1 diagnostic criteria
1.1.1 Western medicine diagnose standard
(5) anovulatory functional bleeding: because ovulation failure, no corpus luteum forms, and endometrial hyperplasia is too much, the irregular metrorrhagia of clinical manifestation, and menstrual period are different in size, and are few for a long time during amount of bleeding, even bleed profusely.Gynecologial examination: cervix uteri hyperemia when hemorrhage, softer, palace mouth pine, uterus are softer, have with a side or the increase of bilateral ovaries capsule.The basal body temperature single phase property, the vaginal exfoliated cell smear anovulatory cycle sexually revises, and hemorrhage preceding 1-2 days cervix uteri mucus presents the lobate crystallization of pteridophyte, and the visible proliferative phase of inner membrance pathologic finding changes or Swiss cheese hyperplasia, and the no secretory phase changes.
(6) ovulation type anovulatory dysfunctional uterine hemorrhage: 1. luteal insufficiency: through preceding endometrial secretion dysfunction; The clinical manifestation menstrual cycle shortens, and how much differs menostaxis through amount; The visible sometimes keratinocyte index of vaginal smear is higher, and cell accumulation, gauffer are not good; The basal body temperature biphasic or bipolar type, shorten luteal phase, below 10 days, or is trapezoidal rising or decline.2. atrophy of corpus iuteum is incomplete, is the secretory phase change through intrauterine film biopsy in the 5th day; Clinical manifestation is that menstrual cycle is normal, and how many menostaxis differs through amount; Basal body temperature is the biphasic or bipolar type that is not true to type, fall delay or decline gradually.
1.1.2 tcm diagnosis standard
1.1.2.1 Chinese medical discrimination: kidney yang deficiency syndrome (with reference to " new Chinese medicine clinical guidance principle ")
(17) hemorrhage suddenly, amount is many or not to the utmost dripping, and color is light or dark red, and matter is rare clearly.
(18) abdominal pain in menstruation, the cold or empty discomfort of weighing down of lower abdomen.
(19) lethargy.
(20) dizzy, stomachache.
(21) shallow complexion.
(22) clear urine in large amounts, big loose stool is thin.
(23) fat light, the white and thin fur of body of the tongue.
(24) deep,thready and forceless pulse.
More than (1), (2) must possess, have concurrently all the other 4 promptly diagnosable.
1.1.2.2 mild symptoms weight classification standard sees Table 24
Table 24
Symptom Gently In Heavy
Primary symptom 2 minutes 4 minutes 6 minutes
Amount of bleeding is many Wrap dripping not to the utmost 5-7 days with paper one every day Wrap dripping not to the utmost 7-10 days with paper two every day Use the paper three guarantees every day, dripping not to the utmost more than 10 days
Abdominal pain in menstruation Stomachache can be stood Stomachache needs to have a rest The thing pain relieving of need taking medicine
Lethargy Fatigue and weak Lassitude Drowsy
Dizzy Idol has dizzy Dizzyly need not have a rest Need bed
Shallow complexion Anhui is white The sallow profit of owing Sallow and dark
Clear urine in large amounts, big loose stool is thin Every day 2-3 time Every day 4-5 time Every day is more than 5 times
Body of the tongue is fat light, white and thin fur Pale tongue, white and thin fur Corpulent tongue matter is light, and tongue is little greasy Enlarged tongue is light, gums, and tongue is greasy in vain
Deep,thready and forceless pulse Carefully unable Heavy unable Heavy carefully unable
Hematochrome 10g 8g 6g
The nail fold microcirculation Slight blood stasis The moderate blood stasis The severe blood stasis
1.1.2.4 state of an illness grade scale:
Slightly: disease integrated value summation 8-18 branch
Moderate: disease integrated value summation 19-36 branch
Severe: disease integrated value summation 〉=37 minutes
1.2 include the case standard in:
In meeting, Western medicine diagnose standard and Chinese medical discrimination typing standard and go up the ring seraglio blood person of increasing, all can include the test case in.
1.3 get rid of the case standard:
(1) confirms by gestation tumor, wound or whole body mathematics disease causer on inspection.
(2) age is person below 14 years old or more than 50 years old, or women breast-feeding their children, to this medicine allergy sufferers.
(7) be associated with serious primary disease such as cardiovascular, liver, kidney and hemopoietic system, psychotic.
(8) do not meet the standard of including in, not medication in accordance with regulations can't be judged that curative effect or data are not congruent to affect the treatment or safety judgement person.
14. observation index:
2.1 safety observation index:
2.1.1 general health check-up project
2.1.2 blood, urine, just routine test
2.1.3 the heart, liver, kidney function test
2.2 health giving quality observation index:
2.2.1 doing well,improving situation
2.2.2 hematochrome is measured
2.2.3 examination of nail fold microcirculation
2.2.4 examination of basal body temperature
2.2.5 B-type ultrasonography
15. EXPERIMENTAL DESIGN
3.1 medicine: spring blood peace capsule (being provided by Tianjin Hongrentang Pharmaceutical Co., Ltd.) is provided test drug
3.8 usage: oral, 1 time 4,3 times on the one.
3.9 the course of treatment: be a course of treatment all around, observed for two courses of treatment continuously.
3.10 treatment requires: do not add during the medication with hemostasis, the pain relieving and the medicine of enriching blood are in order to avoid influence is judged when analyzing curative effect.
3.5 observed and recorded, summary require:
By the clinical study design requirement, unified form is made itemized record, conscientiously finishes writing case history, should note observing untoward reaction, and tracing study.After the off-test, can not alter case history arbitrarily, various data must be done statistical procedures.
16. curative effect determinate standard:
4.3 traditional Chinese medical science disease curative effect determinate standard
4.1.1 clinical recovery: after the control over bleeding, continuous 3 menstrual cycle, menstrual period, blood volume are all normal, and subjective symptoms disappears, and hematochrome can recover normally to ovulate more than 10g, is no less than 12 days luteal phase.
4.1.2 produce effects: after the control over bleeding, menstrual cycle, blood volume are normal substantially, but menstrual period still at 7-10 days, subjective symptoms disappears substantially, hematochrome is the above person of 10g.
4.1.3 effectively: menstrual cycle, menstrual period, part subjective symptoms be improved significantly, oligemia, hematochrome is the above person of 8g.
4.1.4 it is invalid: above every improvement of all not having.
4.2 safety evaluatio standard
One-level: safety, there is not any untoward reaction.
Secondary: compare safety,, need not do any processing, can continue administration if any untoward reaction.
Three grades: safety problem is arranged, moderate untoward reaction is arranged, can continue administration after processing.
Level Four: because of test is ended in untoward reaction.
17. statistical procedures:
Measurement data adopts the t check
18. interpretation of result:
6.1 efficacy analysis sees Table 25
Table 25
The example number Recovery from illness Produce effects Effectively Invalid
The symptom curative effect 300 108 102 84 6
36 34 28 2
Marriage
Married 141 50 47 39 5
Unmarried 159 58 55 45 1
The all ages and classes curative effect
20< 138 48 44 45 1
20- 88 26 29 31 2
30- 37 18 16 2 1
40- 37 16 13 6 2
Different course of disease curative effects
5 years< 117 43 40 33 1
5-9 86 31 30 24 1
10-14 73 27 25 19 2
More than 15 years 24 7 7 8 2
Different state of an illness curative effects
Gently 163 59 56 47 1
In 98 36 34 26 2
Heavy 39 13 12 11 3
6.2 the cardinal symptom integral analysis (X ± SD) that sees Table 26 before and after the treatment
Symptom The example number Before the treatment After the treatment Front and back are poor The P value
Amount of bleeding is many 300 4.32±1.03 3.26±0.86 1.06±0.17 <0.05
Abdominal pain in menstruation 300 5.16±2.12 3.87±1.64 1.29±0.48 <0.05
Lethargy 204 3.24±1.28 2.01±0.36 1.23±0.92 <0.05
Dizzy 184 4.27±1.36 3.01±1.02 1.26±0.39 <0.05
Shallow complexion 195 3.28±2.12 2.67±1.64 0.61±0.48 <0.05
6.3 the hematochrome integral analysis (X ± SD) that sees Table 27 before and after the treatment
The example number Before the treatment After the treatment Front and back are poor P
300 3.04±0.56 2.17±0.50 0.87±0.06 <0.01
6.4 the nail fold microcirculation improvement situation (X ± SD) that sees Table 28 before and after the treatment
The example number Before the treatment After the treatment Front and back are poor P
300 5.02±1.23 3.84±1.02 1.18±0.21 <0.01
6.5 safety indexes detects and sees Table 29 before and after the treatment
Before the treatment After the treatment
Routine blood test Normally 300 300
Unusually 0 0
Routine urinalysis Normally 300 300
Unusually 0 0
Just conventional Normally 300 300
Unusually 0 0
Rabat Normally 300 300
Unusually 0 0
Electrocardiogram Normally 300 300
Unusually 0 0
GPT Normally 300 300
Unusually 0 0
BUN Normally 300 300
Unusually 0 0
Cr Normally 300 300
Unusually 0 0
Hepatic and renal function is had no effect safe without toxic side effect after the clinical practice of table 6 explanation spring blood peace capsule.
19. untoward reaction
This tests no any untoward reaction among the 300 routine patients, and the safety evaluatio standard is an one-level.
20. rejecting case
2 examples are rejected in this test altogether, and an example is for merging with the hemostasis Western medicine; One example is a therapy discontinued, so rejected.
21. follow up a case by regular visits to
The above case of produce effects is carried out following up a case by regular visits in three months statistics see Table 30
The example number Follow up a case by regular visits to case load Recurrence Not recurrence
210 80 0 80
22. discuss, brief summary: the spring blood peace capsule of producing by Tianjin Hongrentang Pharmaceutical Co., Ltd. have kidney tonifying solid in, the effect of regulating menstruation, hemostasis.Main term is because of deficiency of the liver and kindey, the menorrhagia due to the Chong and Ren channel disorder, and abdominal pain in menstruation, the adolescence dysfunctional uterine bleeding, last ring is the metrorrhagia person afterwards.The clinical observation to above disease 300 routine patients is passed through by my institute, prove that this product has significantly curative effect to improving above symptom and increasing aspects such as hematochrome, promotion microcirculation, treatment anteroposterior diameter statistical procedures P<0.05, and it is reliable by its safety of clinical proof, human body is had no side effect, should extensively promote the use of.
Test unit: person: Liang Wenyan (associate chief physician) is responsible in the test of the hospital of traditional Chinese hospital, Tianjin
Test participant: Fan Ruihong (associate chief physician), Ma Lianzhen (main chief physician)
The specific embodiment
Embodiment 1: capsule
Take by weighing raw material by following weight proportion:
Radix Rehmanniae Preparata 300g Semen Plantaginis (processed with salt) 120g Poria 150g Radix Bupleuri 100g Radix Achyranthis Bidentatae 150g Fructus Schisandrae Chinensis (system) 150g Cortex Cinnamomi 60g Rhizoma Alismatis 100g Radix Notoginseng; 100g Radix Aconiti Lateralis Preparata (system) 60g medicine 120g Rhizoma Coptidis 30g Cortex Moutan 100g
Preparation method:
1. Radix Aconiti Lateralis Preparata, Radix Notoginseng, Radix Bupleuri, Cortex Cinnamomi, Rhizoma Coptidis powder are broken into fine powder, cross 80 mesh sieves, standby;
2. with Radix Rehmanniae Preparata, Poria, Rhizoma Alismatis, Semen Plantaginis, Radix Achyranthis Bidentatae, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae, Cortex Moutan water extraction three times, add 6 times of water gagings for the first time, extract 3h; Add for the second time 5 times of water gagings, extract 2h; Add 4 times of water gagings for the third time, extract 1h, merge extractive liquid, filters, and filtrate is condensed into the clear paste that relative density is 1.25~1.30 (65-70 ℃ of heat is surveyed);
3. above-mentioned clear paste is added the fine powder after pulverizing, mixing, drying is ground into fine powder, crosses 24 mesh sieves, and the hard capsule of packing into is made 1160 of capsules, every capsules content of dispersion 1.02~1.32g, promptly.Oral, one time 4,3 times on the one, or follow the doctor's advice.
Embodiment 2: tablet
Take by weighing raw material by following weight proportion:
Radix Rehmanniae Preparata 150g Semen Plantaginis (processed with salt) 60g Poria 75g Radix Bupleuri 50g Radix Achyranthis Bidentatae 75g Fructus Schisandrae Chinensis (system) 75g Cortex Cinnamomi 30g Rhizoma Alismatis 50g Radix Notoginseng 50g Radix Aconiti Lateralis Preparata (system) 30g Rhizoma Dioscoreae 60g Rhizoma Coptidis 15g Cortex Moutan 50g starch is an amount of
Preparation method:
1. Radix Aconiti Lateralis Preparata, Radix Notoginseng, Radix Bupleuri, Cortex Cinnamomi, Rhizoma Coptidis powder are broken into fine powder, cross 80 mesh sieves, standby;
2. Radix Rehmanniae Preparata, Poria, Rhizoma Alismatis, Semen Plantaginis, Radix Achyranthis Bidentatae, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae, Cortex Moutan are used
Water extraction three times adds 6 times of water gagings for the first time, extracts 3h; Add for the second time 5 times of water gagings, extract 2h; Add 4 times of water gagings for the third time, extract 1h, merge extractive liquid, filters, and filtrate is condensed into the clear paste that relative density is 1.2 5~1.30 (65-70 ℃ of heat is surveyed);
3. above-mentioned clear paste is added the fine powder after pulverizing, mixing, it is an amount of to add starch again, and mixed powder is broken into fine powder, crosses 100 mesh sieves, is pressed into 690, and every be the substrate of 1.50g~1.94g, employing polyvinyl alcohol bag film-coat, promptly.Oral, one time 4,3 times on the one.
Embodiment 3: granule
Take by weighing raw material by following weight proportion:
Radix Rehmanniae Preparata 450g Semen Plantaginis (processed with salt) 180g Poria 225g Radix Bupleuri 150g Radix Achyranthis Bidentatae 225g Fructus Schisandrae Chinensis (system) 225g Cortex Cinnamomi 90g Rhizoma Alismatis 150g Radix Notoginseng 150g Radix Aconiti Lateralis Preparata (system) 90g Rhizoma Dioscoreae 180g Rhizoma Coptidis 45g Cortex Moutan 150g
Preparation method:
With Radix Aconiti Lateralis Preparata, Radix Notoginseng, Radix Bupleuri, Cortex Cinnamomi, Rhizoma Coptidis, Radix Rehmanniae Preparata, Poria, Rhizoma Alismatis, Semen Plantaginis,
Radix Achyranthis Bidentatae, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae, Cortex Moutan water extraction three times add 8 times of water gagings for the first time, extract 3h; Add for the second time 6 times of water gagings, extract 2h; Add 6 times of water gagings for the third time, extract 1h, merge extractive liquid, filters, and filtrate is condensed into the clear paste that relative density is 1.25~1.30 (65-70 ℃ of heat is surveyed);
2. above-mentioned clear paste is added ethanol and make and contain the alcohol amount and reach 70%, stir evenly, standing over night is got supernatant, reclaims ethanol, is condensed into relative density and is 1.38~1.41 clear paste.
3. qinghuo reagent, it is an amount of to add equivalent sucrose, dextrin and ethanol, makes granule, drying; Or qinghuo reagent, add dextrin, correctives is an amount of, mixing, spray drying is made sugar-free granule 800g, promptly.Oral, one time 1 bag, every packed 10g, 2 times on the one.

Claims (3)

1, a kind of kidney tonifying CHONG meridian stabilizing and menstruation regulating haemostatic medicament is characterized in that it is the medicament of being made by following materials of weight proportions medicine
10~30 parts of Radix Bupleuri 10-40 of Radix Rehmanniae Preparata 50-80 part Semen Plantaginis 10-30 part Poria part
10~20 parts of 5~15 portions of Rhizoma Alismatis of 20~50 portions of Cortex Cinnamomis of 20~50 parts of Fructus Schisandrae Chinensis of Radix Achyranthis Bidentatae
5~10 parts of 15~30 portions of Rhizoma Coptidis of 9~15 portions of Rhizoma Dioscoreaes of Radix Notoginseng 10-30 part Radix Aconiti Lateralis Preparata
Cortex Moutan 10-30 part.
2, kidney tonifying CHONG meridian stabilizing and menstruation regulating haemostatic medicament according to claim 1 is characterized in that it is the medicament of being made by following materials of weight proportions medicine
30 parts of 20 parts of Radix Achyranthis Bidentataes of 30 parts of Radix Bupleuri of 24 parts of Poria of 60 portions of Semen Plantaginiss of Radix Rehmanniae Preparata
12 parts of 20 parts of Radix Aconiti Lateralis Preparatas of 20 portions of Radix Notoginseng of 12 portions of Rhizoma Alismatis of 30 portions of Cortex Cinnamomis of Fructus Schisandrae Chinensis
20 parts of 6 parts of Cortex Moutans of 24 portions of Rhizoma Coptidis of Rhizoma Dioscoreae.
3, kidney tonifying CHONG meridian stabilizing and menstruation regulating haemostatic medicament according to claim 1 is characterized in that said medicament is capsule, granule, tablet.
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CN103830684B (en) * 2014-03-24 2016-02-03 雷现莲 One treats menorrheal pharmaceutical composition and application thereof
CN104524116A (en) * 2015-02-01 2015-04-22 胡文杰 Traditional Chinese medicine composition for treating kidney deficiency and blood stasis type endometrial hyperplasia
CN105535620A (en) * 2016-01-13 2016-05-04 岳晓燕 Traditional Chinese medicine decoction for treating dysmenorrhea

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卫生部药品标准中药成方制剂第18册. 卫生部药典委员会,222,卫生部药典委员会. 1998 *

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